Background Citrullination by the periodontal pathogen Porphyromonas gingivalis has been hypothesized to play a role in RA aetiology, by contributing to the production of anti-citrullinated protein antibodies (ACPA). We have previously shown that the ACPA response precedes RA by several years, and we have recently demonstrated elevated anti-P. gingivalis antibody levels in patients with RA compared with controls (1–3).
Objectives The aim of the present study was to investigate the link between P.gingivalis and RA further, by analysing whether anti-P. gingivalis antibodies predate RA diagnosis and ACPA production.
Methods A case-control study was performed within the Medical Biobank and the Maternity cohort of Northern Sweden including 251 individuals who had donated 422 blood samples predating the onset of symptoms of RA, and 198 population-based controls from the same cohorts. The median (IQR) predating time until onset of symptoms was 5.2 (6.2) years. For 192 individuals diagnosed with RA, blood samples were available from the time of diagnosis. Samples were analysed using in-house ELISAs for presence of antibodies to the virulence factor arginine gingipainB (RgpB) purified from P. gingivalis, and to a citrullinated peptide (CPP3) derived from the P. gingivalis peptidylarginine deiminase enzyme P.PAD.
Results The concentration of anti-RgpB IgG levels was significantly increased in pre-symptomatic individuals (mean±SEM; 152.7±14.8 AU/ml) and in RA patients (114.4±16.9 AU/ml), compared with controls (82.2±12.1 AU/ml, p<0.001 for both). Antibodies against CPP3 were detected in 5% of the pre-symptomatic individuals and in 8% of the RA-patients, with elevated levels in both pre-symptomatic individuals (4.33±0.59 AU/ml) and RA-patients (9.29±1.81 AU/ml) compared with controls (2.36±0.58 AU/ml, p<0.001 for both). The anti-CPP3 antibody response followed the ACPA response, with increasing antibody concentrations over time, whilst the anti-RgpB IgG response was elevated and stable in pre-symptomatic individuals during the pre-dating time and showed a trend towards lower levels after RA diagnosis.
Conclusions Anti-P. gingivalis antibody concentrations were significantly increased in RA compared with controls and these antibodies were detected years before the onset of symptoms of RA, supporting an aetiological role for P. gingivalis in the development of RA.
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Disclosure of Interest None declared